Tetraspanins are a family of membrane glycoproteins found in all multicellular eukaryotes. Also called tetraspans or the transmembrane 4 superfamily (TM4SF), these proteins have four transmembrane domains, intracellular N and C-termini and two extracellular domains. Generally, tetraspanins are often thought to act as scaffolding proteins, anchoring multiple proteins to one area of the cell membrane. (Boucheix C. and Rubinstein E., 2001; Charrin, S. et al., 2009)
Tetraspanins are highly conserved between species. D6.1, the rat homologue of Co-029, present 74.2% homology in the nucleotide and a 70% homology in the amino acid sequence with Co-029 (Claas et al., 1998). Tetraspanins display numerous properties that indicate their physiological importance in cell adhesion, motility, activation and proliferation, as well as their contribution to pathological conditions such as metastasis.
Clinical studies have reported a link between tetraspanins and cancer and metastatic development. Particularly the level of expression of certain tetraspanins in a cancer is correlated with metastatic formation. More particularly, recent studies showed that the Co-029 tetraspanin expression is correlated with an increase of the metastasis potential in rat models of digestive tract tumors (Claas et al, 1998), in human liver (Kanetaka K. et al, 2003) and esophagus tumors (Zhou et al, 2008). More particularly, the inventors showed that the Co-029 tetraspanin was strongly expressed in metastatic cell lines of a colorectal carcinoma whereas it was absent on cells of the primary tumor (Le Naour, F. 2006). However there is no real demonstration of the direct role of Co-029 in metastatic development.
Immunohistochemical studies and transcriptional data suggest that in normal tissues and their malignant counterparts, the tetraspanin Co-029 is expressed mainly in the digestive tract including colorectal epithelium, oesophagus, liver and pancreas but it may also be found in prostate or trachea.
The restricted expression of Co-029 and its absence from circulating blood cells together with its expression on major tumor types with a relation to adverse prognosis suggest that it could be appropriately targeted for the treatment of cancer.
There is still a need for improving the management of treatment for cancer and cancer metastasis. Thus targeting the Co-029 pathway could be an interesting approach for therapeutic strategies in this domain.